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Understanding the intricate relationships between diseases is critical for both prevention and recovery. However, there is a lack of suitable methodologies for exploring the precedence relationships within multiple censored time-to-event data, resulting in decreased analytical accuracy. This study introduces the Censored Event Precedence Analysis (CEPA), which is a nonparametric Bayesian approach suitable for understanding the precedence relationships in censored multivariate events. CEPA aims to analyze the precedence relationships between events to predict subsequent occurrences effectively. We applied CEPA to neonatal data from the National Health Insurance Service, identifying the precedence relationships among the seven most commonly diagnosed diseases categorized by the International Classification of Diseases. This analysis revealed a typical diagnostic sequence, starting with respiratory diseases, followed by skin, infectious, digestive, ear, eye, and injury-related diseases. Furthermore, simulation studies were conducted to demonstrate CEPA suitability for censored multivariate datasets compared to traditional models. The performance accuracy reached 76% for uniform distribution and 65% for exponential distribution, showing superior performance in all four tested environments. Therefore, the statistical approach based on CEPA enhances our understanding of disease interrelationships beyond competitive methodologies. By identifying disease precedence with CEPA, we can preempt subsequent disease occurrences and propose a healthcare system based on these relationships. [ABSTRACT FROM AUTHOR]

Traditionally, datasets with multiple censored time-to-events have not been utilized in multivariate analysis because of their high level of complexity. In this paper, we propose the Censored Time Interval Analysis (CTIVA) method to address this issue. It estimates the joint probability distribution of actual event times in the censored dataset by implementing a statistical probability density estimation technique on the dataset. Based on the acquired event time, CTIVA investigates variables correlated with the interval time of events via statistical tests. The proposed method handles both categorical and continuous variables simultaneously—thus, it is suitable for application on real-world censored time-to-event datasets, which include both categorical and continuous variables. CTIVA outperforms traditional censored time-to-event data handling methods by 5% on simulation data. The average area under the curve (AUC) of the proposed method on the simulation dataset exceeds 0.9 under various conditions. Further, CTIVA yields novel results on National Sample Cohort Demo (NSCD) and proteasome inhibitor bortezomib dataset, a real-world censored time-to-event dataset of medical history of beneficiaries provided by the National Health Insurance Sharing Service (NHISS) and National Center for Biotechnology Information (NCBI). We believe that the development of CTIVA is a milestone in the investigation of variables correlated with interval time of events in presence of censoring. [ABSTRACT FROM AUTHOR]

This review paper provides an extensive analysis of the rapidly evolving convergence of deep learning and long non-coding RNAs (lncRNAs). Considering the recent advancements in deep learning and the increasing recognition of lncRNAs as crucial components in various biological processes, this review aims to offer a comprehensive examination of these intertwined research areas. The remarkable progress in deep learning necessitates thoroughly exploring its latest applications in the study of lncRNAs. Therefore, this review provides insights into the growing significance of incorporating deep learning methodologies to unravel the intricate roles of lncRNAs. By scrutinizing the most recent research spanning from 2021 to 2023, this paper provides a comprehensive understanding of how deep learning techniques are employed in investigating lncRNAs, thereby contributing valuable insights to this rapidly evolving field. The review is aimed at researchers and practitioners looking to integrate deep learning advancements into their lncRNA studies. [ABSTRACT FROM AUTHOR]

Structures of the GABA B receptor in inactive (light orange and light green) and active (orange and green) states are shown with Cryo-EM maps (gray) in the same orientation. • Cryo-EM structures for the inactive and active GABA B receptor were determined. • TM domains interact through TM3 and TM5 in an open conformation in the inactive state. • GABA binding reorients TM domains to form a TM5/6–TM6′/7′ interface in a closed conformation. • PAM binding between TM6 and TM6 stabilizes the active TM domain conformation. • The relayed structural rearrangement from VFTs to TMs via a linker and ECL2 may be conserved among all class C GPCRs. The neurotransmitter γ-aminobutyric acid (GABA) activates the metabotropic GABA B receptor to generate slow, prolonged inhibitory signals that regulate the neural circuitry. The GABA B receptor is an obligate heterodimeric G protein-coupled receptor (GPCR) comprised of GBR1 and GBR2 subunits, each with extracellular, seven-helix transmembrane (7TM), and coiled-coil domains. To understand how GABA-driven conformational changes in the extracellular domain are transmitted to the 7TM domain during signal transduction, we determined cryo-electron microscopy (EM) structures of GABA B in two different states: an antagonist-bound inactive state, and an active state in which both the GABA agonist and a positive allosteric modulator (PAM) are bound. In the inactive state, the TM3 and TM5 helices in the two 7TM domains engage in cholesterol-mediated as well as direct interactions, resulting in an open conformation. GABA binding forces the extracellular domains of GBR1 and GBR2 into a compact form, relocating the linkers that connect the extracellular and 7TM domains closer to each other. The movement of the linker along with the associated extracellular loop 2 of the 7TM domain reorients the two 7TM domains and creates a new interface with the TM5, TM6 and TM7 helices in a closed conformation. PAM binding to the interface between the TM6 and TM6 helices stabilizes the active 7TM domain conformation. The relayed structural rearrangement results in significant conformational changes in the TM helices, as well as intracellular loop 3 in GBR2, which may promote the binding and activation of the Gi/o proteins. [ABSTRACT FROM AUTHOR]

In general survival analysis, multiple studies have considered a single failure time corresponding to the time to the event of interest or to the occurrence of multiple events under the assumption that each event is independent. However, in real-world events, one event may impact others. Essentially, the potential structure of the occurrence of multiple events can be observed in several survival datasets. The interrelations between the times to the occurrences of events are immensely challenging to analyze because of the presence of censoring. Censoring commonly arises in longitudinal studies in which some events are often not observed for some of the subjects within the duration of research. Although this problem presents the obstacle of distortion caused by censoring, the advanced multivariate survival analysis methods that handle multiple events with censoring make it possible to measure a bivariate probability density function for a pair of events. Considering this improvement, this paper proposes a method called censored network estimation to discover partially correlated relationships and construct the corresponding network composed of edges representing non-zero partial correlations on multiple censored events. To demonstrate its superior performance compared to conventional methods, the selecting power for the partially correlated events was evaluated in two types of networks with iterative simulation experiments. Additionally, the correlation structure was investigated on the electronic health records dataset of the times to the first diagnosis for newborn babies in South Korea. The results show significantly improved performance as compared to edge measurement with competitive methods and reliability in terms of the interrelations of real-life diseases. [ABSTRACT FROM AUTHOR]

"These authors contributed equally: Yoojoong Kim, Jong-Ho Kim, Hyung Joon Joo and Sanghoun Song." now reads: "These authors contributed equally: Yoojoong Kim and Jong-Ho Kim. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-17806-8, published online 16 August 2022 The original version of this Article contained errors in the Author Information section. [Extracted from the article]

Motivation: Despite the potential usefulness, the association analysis of gene expression with interval times of two events has been hampered because the occurrence of events can be censored and the conventional survival analysis is not suitable to handle two censored events. However, the recent advances of multivariate survival analysis considering multiple censored events together provide an unprecedented chance for this problem. Based on such advances, we have developed a software tool, GAIT, for the association analysis of gene expression with interval time of two events. Results: The performance of GAIT was demonstrated by simulation studies and the real data analysis. The result indicates the usefulness of GAIT in a wide range of biomedical applications. [ABSTRACT FROM AUTHOR]

AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 models of the σ 2 and serotonin 2A (5-HT2A) receptors, testing hundreds of new molecules and comparing results with those obtained from docking against the experimental structures. Hit rates were high and similar for the experimental and AF2 structures, as were affinities. Success in docking against the AF2 models was achieved despite differences between orthosteric residue conformations in the AF2 models and the experimental structures. Determination of the cryo-electron microscopy structure for one of the more potent 5-HT2A ligands from the AF2 docking revealed residue accommodations that resembled the AF2 prediction. AF2 models may sample conformations that differ from experimental structures but remain low energy and relevant for ligand discovery, extending the domain of structure-based drug design.

Diabetes mellitus, a prevalent metabolic disorder, is associated with a multitude of complications that necessitate vigilant management post-diagnosis. A notable complication, diabetic retinopathy, could lead to intense ocular injury, including vision impairment and blindness, due to the impact of the disease. Studying the transition from diabetes to diabetic retinopathy is paramount for grasping and halting the progression of complications. In this study, we examine the statistical correlation between type 2 diabetes mellitus and retinal disorders classified elsewhere, ultimately proposing a comprehensive disease network. The National Sample Cohort of South Korea, containing approximately 1 million samples and primary diagnoses based on the International Statistical Classification of Diseases and Related Health Problems 10th Revision classification, was utilized for this retrospective analysis. The diagnoses of both conditions displayed a statistically significant correlation with a chi-square test value of P < .001, and the t test for the initial diagnosis date also yielded a P < .001 value. The devised network, comprising 27 diseases and 142 connections, was established through statistical evaluations. This network offers insight into potential pathways leading to diabetic retinopathy and intermediary diseases, encouraging medical researchers to further examine various risk factors associated with these connections., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Electrocardiography (ECG)-based diagnosis by experts cannot maintain uniform quality because individual differences may occur. Previous public databases can be used for clinical studies, but there is no common standard that would allow databases to be combined. For this reason, it is difficult to conduct research that derives results by combining databases. Recent commercial ECG machines offer diagnoses similar to those of a physician. Therefore, the purpose of this study was to construct a standardized ECG database using computerized diagnoses., Methods: The constructed database was standardized using Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) and Observational Medical Outcomes Partnership-common data model (OMOP-CDM), and data were then categorized into 10 groups based on the Minnesota classification. In addition, to extract high-quality waveforms, poor-quality ECGs were removed, and database bias was minimized by extracting at least 2,000 cases for each group. To check database quality, the difference in baseline displacement according to whether poor ECGs were removed was analyzed, and the usefulness of the database was verified with seven classification models using waveforms., Results: The standardized KURIAS-ECG database consists of high-quality ECGs from 13,862 patients, with about 20,000 data points, making it possible to obtain more than 2,000 for each Minnesota classification. An artificial intelligence classification model using the data extracted through SNOMED-CT showed an average accuracy of 88.03%., Conclusions: The KURIAS-ECG database contains standardized ECG data extracted from various machines. The proposed protocol should promote cardiovascular disease research using big data and artificial intelligence.

Background: A computerized 12-lead electrocardiogram (ECG) can automatically generate diagnostic statements, which are helpful for clinical purposes. Standardization is required for big data analysis when using ECG data generated by different interpretation algorithms. The common data model (CDM) is a standard schema designed to overcome heterogeneity between medical data. Diagnostic statements usually contain multiple CDM concepts and also include non-essential noise information, which should be removed during CDM conversion. Existing CDM conversion tools have several limitations, such as the requirement for manual validation, inability to extract multiple CDM concepts, and inadequate noise removal., Objectives: We aim to develop a fully automated text data conversion algorithm that overcomes limitations of existing tools and manual conversion., Methods: We used interpretations printed by 12-lead resting ECG tests from three different vendors: GE Medical Systems, Philips Medical Systems, and Nihon Kohden. For automatic mapping, we first constructed an ontology-lexicon of ECG interpretations. After clinical coding, an optimized tool for converting ECG interpretation to CDM terminology is developed using term-based text processing., Results: Using the ontology-lexicon, the cosine similarity-based algorithm and rule-based hierarchical algorithm showed comparable conversion accuracy (97.8 and 99.6%, respectively), while an integrated algorithm based on a heuristic approach, ECG2CDM, demonstrated superior performance (99.9%) for datasets from three major vendors., Conclusion: We developed a user-friendly software that runs the ECG2CDM algorithm that is easy to use even if the user is not familiar with CDM or medical terminology. We propose that automated algorithms can be helpful for further big data analysis with an integrated and standardized ECG dataset., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The fact that medical terms require special expertise and are becoming increasingly complex makes it difficult to employ natural language processing techniques in medical informatics. Several human-validated reference standards for medical terms have been developed to evaluate word embedding models using the semantic similarity and relatedness of medical word pairs. However, there are very few reference standards in non-English languages. In addition, because the existing reference standards were developed a long time ago, there is a need to develop an updated standard to represent recent findings in medical sciences., Objective: We propose a new Korean word pair reference set to verify embedding models., Methods: From January 2010 to December 2020, 518 medical textbooks, 72,844 health information news, and 15,698 medical research articles were collected, and the top 10,000 medical terms were selected to develop medical word pairs. Attending physicians (n=16) participated in the verification of the developed set with 607 word pairs., Results: The proportion of word pairs answered by all participants was 90.8% (551/607) for the similarity task and 86.5% (525/605) for the relatedness task. The similarity and relatedness of the word pair showed a high correlation (ρ=0.70, P<.001). The intraclass correlation coefficients to assess the interrater agreements of the word pair sets were 0.47 on the similarity task and 0.53 on the relatedness task. The final reference standard was 604 word pairs for the similarity task and 599 word pairs for relatedness, excluding word pairs with answers corresponding to outliers and word pairs that were answered by less than 50% of all the respondents. When FastText models were applied to the final reference standard word pair sets, the embedding models learning medical documents had a higher correlation between the calculated cosine similarity scores compared to human-judged similarity and relatedness scores (namu, ρ=0.12 vs with medical text for the similarity task, ρ=0.47; namu, ρ=0.02 vs with medical text for the relatedness task, ρ=0.30)., Conclusions: Korean medical word pair reference standard sets for semantic similarity and relatedness were developed based on medical documents from the past 10 years. It is expected that our word pair reference sets will be actively utilized in the development of medical and multilingual natural language processing technology in the future., (©Yunjin Yum, Jeong Moon Lee, Moon Joung Jang, Yoojoong Kim, Jong-Ho Kim, Seongtae Kim, Unsub Shin, Sanghoun Song, Hyung Joon Joo. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 24.06.2021.)